The objective of this research is to develop new potential cancer chemotherapeutic agents, based on: 1. biochemical rationale, and 2. the "dual antagonist" concept. Inhibitors of DNA biosynthesis are synthesized which are designed to combine two different but synergistic metabolic inhibitory activities, or, alternatively, chemotherapeutic activity with radiation potentiating or immunogenic effects. The new agents will be studied in isolated enzyme systems, microbiological and tissue culture assays as well as against transplanted, virus induced and carcinogen-induced rodent tumors. Radiobiologic and hypersensitization studies will be conducted, in the hope that more selective radiation potentiating or immunogenic agents will be found. Chemical reaction mechanism and biochemical mode of action studies will be conducted to elucidate the basis of structure-activity relationships and to help in the rational design of more effective agents.